Download File - Mr. Shanks` Class

T.A. Blakelock High School
Grade 11 Biology
Genetics
Mr. Shanks' Class
NaMe:_________________________
Period:_________________________
DNA
Deoxyribonucleic acid (DNA) is a polynucleotide (a
molecule composed of a chain of nucleotides).
 a phosphate
Each nucleotide consists of:
 a nitrogen base
 a sugar
A molecule of DNA is composed of two polynucleotide chains held together by: e
In DNA, adenine always bonds with ___________ with ____ H bonds, and
cytosine always bonds to _____________ with ___H bonds
_________ ___________ and _________ _________ discovered the structure of
DNA
A molecule of DNA is composed of two polynucleotide chains held together by
hydrogen bonds between the bases. Covalent bonds hold each sugar to the
phosphate of the adjacent nucleotide.
DNA has __________ regions known as _____ that determine the _____________
characteristics of an organism
An ____________ in the DNA sequence is known as a _______________
_______________ may be caused by:
Mutations can also occur during the _________________ _____________
DNA Replication:
The structure of DNA allows it to be easily replicated (copied).
The DNA molecule “unzips” and each side serves as a template.
On each half of the molecule, a new complementary half is built.
The two new DNA molecules are identical to each other.
DNA Replication and Cell Division
DNA must _________________ so that during cell division, the new cells formed
each receive a _____________________ of genetic information
Cells must divide for:
_________________ (e.g. unicellular organisms)
_________________ (e.g. 1 fertilized egg --> human of ~100 trillion cells)
_____________ and tissue repair (e.g to replace dead or damaged cells)
Mitosis & the Cell Cycle
Mitosis occurs when a parent cell divides to produce two ____________ daughter cells
____________ refers to the process of dividing the nuclear material
______________ refers to the process of separating the cytoplasm
and its contents into equal
parts
The _________________ consists of mitosis, cytokinesis and interphase
Interphase
G1 phase: _______________
S phase: DNA is _____________
G2 phase: cell prepares for __________
DNA is visible in the nucleus as
strands called _____________
Mitosis
Phase 1 of Mitosis: Prophase
__________ move to opposite poles of the cell
__________ condenses and shortens into chromosomes
____________________ form between the centrioles
Nuclear membranes starts to ________________
Phase 2 of Mitosis: Metaphase
Spindle fibres attached to _______________
pull chromosomes into place
Chromosomes line up across
the _____________of the cell
Centrioles __________________
Phase 3 of Mitosis: Anaphase
_____________ separate at the centromere
________________ chomosomes are pulled to
opposite poles by spindle fibres contracting
Phase 4 of Mitosis: Telophase
Two _______________ envelopes form
Single-stranded chromosomes ______________
to become chromatin
________________ occurs after telophase:
______________________ are distributed
between the two daughter cells and
the cell membrane ___________inward
Meiosis vs mitosis
The purpose of mitosis is to maintain ____________________________
(the number of chromosomes in each daughter cell stays the same)
The purpose of meiosis is to __________________ (sex cells) which unite during sexual
reproduction (the number of chromosomes in each sex cell is half of parent cell)
Asexual & Sexual reproduction
Asexual reproduction is any reproduction that does NOT involve _______________.
Sexual reproduction is any reproduction that does involve ____________________.
Asexual Reproduction
1. A _________________ parent gives rise to offspring that are
genetically _______________________ to the original parent (clones).
2. Often produces many offspring ____________________
3. There are no ________________________ structures required by the parent.
For example:
__________________ of Amoeba; ________________ in yeast;
__________________ of sea stars; _______________ formation by ferns
__________________ propagation by strawberries;
Sexual Reproduction
Genetic information from ____________ cells is combined to produce a new organism
(offspring are genetically ________________ from parent)
Requires more ______________ and ________________ than asexual reproduction
Sexually reproducing organisms are better able to adapt to ____________________
environments because of differences between individuals
Individuals that are better __________________ will survive and perpetuate the species
Parthenogenesis
Sexual reproduction involving ____________________ individual
Egg is made by meiosis and then it duplicates its chromosomes
without being ___________________________
common in lizards & _________________________ in deserts
Phase and details of Meiosis I and results of Meiosis II
__________PHASE
__________________ chromatin
___________ membrane
EARLY ___________PHASE I
1. the chromatin ________________ and
is visible as thin 2-stranded ____________
2. the _______________ membrane disappears
MID _______PHASE I
1. the chromosomes continue to ________________ and
are now visible as 4-stranded _____________
2. the tetrad consists of two ___________chromosomes,
one from each parent, called ___________ chromosomes
3. ______________ duplicates
Meiosis I – The Breakdown
-All of the Chromosomes here have already been ____________ before meiosis begins.
- The Big Chromosomes here represent one _____________ pair
- The little chromosomes are also one _______________ pair
of a different chromosome.
-The black chromosomes came from one _____________, the
grey from the other.
LATE _____PHASE I
1. pieces of the_______________ pair break and exchange
segments with other strands in __________________
2. the structures are now called _________________
as many are _____________-shaped
_______ PHASE I
1.
_______________ move to the poles
2. spindle fibres attach to the _______________
3. ______________ pairs are pulled to the
cell ___________ by the contracting spindle fibres
_______PHASE I
1. spindle fibres contract _________________
the homologus pairs
2. ____________________ chromosomes are
pulled to opposite poles
______PHASE I
1. the ____________________ pair of chromosomes
are fully separated
2. The _____________ chromatids remains together.
3. the ______________ membrane re-appears
4. the _____________ and spindle fibres disappear
__________PHASE II, the end of meiosis
1. Meiosis II proceeds just like mitosis, but with ________________ as many
double-stranded chromosomes
2. The final product is __ __________________ cells each with single-stranded
chromosomes due to ____________ __________________ [pg 135]
Meiosis II – The Breakdown
1. Independent __________________________ refers to the way that chromosomes line up on the Metaphase II plate.
2. Note how each of the cells below has one copy of the larger ____________________
and one copy of the smaller.
These cells are _____________ because they have one of each.
NOT because of THIS difference 
Terms for cells:
diploid [2N]:
__________________ of information or chromosomes
haploid [1N]: __________________ of information or chromosomes
all cells are ______________ prior to meiosis
at the end of meiosis I, the two sets of information or chromosomes has been
____________________ to one set
[______________  __________________]
Chromosomes and Genes

Within each human somatic cell there are ________________________________________

Karyotype of metaphase chromosomes

Each chromosome is made of ______________

Long strands of chromatin are packed tightly together to
make ________________________

A segment of DNA is called a _________________

Each chromosome contains many genes


A pair of homologous chromosomes have the same genes but the specific information may differ
slightly
For example: this homologous pair contains the
gene for eye colour; but one chromosome has the
gene for brown eyes, while the other has the gene
for blue eyes

A = _________________________; a = _________________________

These are called _________________________ (the different forms of expression of a gene)

Some alleles are dominant, while others are recessive

If a person has the dominant and recessive alleles (______________________________), only
the dominant will be observed in their phenotype

If a person has 2 dominant or 2 recessive alleles, their genotype is _____________________

Genotype = the specific alleles a person has (e.g. ______________)

Phenotype = the observable traits a person has (e.g. ________________________)

E.g.
Mendelian Genetics
Early Ideas About Heredity
People knew that ____________ and ____________ transmitted information about traits
Blending theory offspring were the __________________of their parents
Problem:
Would expect variation to _______________________
But variation in traits _____________________
Gregor Mendel
Strong background in plant ______________ and ____________________
Using pea plants, found indirect but observable evidence of how parents _________
_______ to offspring
Why The Garden Pea Plant?
1.
2.
3.
4.
Mendel's First Experiment
He crossbred pure ________ and pure _______ plants.
These plants were called the __________ generation (_____).
This experiment is called a ____________ cross because it focuses on only _______
characteristic.
Mendel's Hypothesis: Mendel expected to see offspring plants of ____________ height
The hybrid offspring from P were called _____________ ____________ (_____).
Mendel's Observations: All of the offspring were __________.
Mendel's Conclusion:
_____________ trait = tallness,
________ trait = shortness,
the _____________ trait not expressed in first generation
The Principle of Dominance:
When an organism is hybrid (crossbred) for a pair of contrasting traits, it shows only the _______
trait.
Mendel's Second Experiment
Mendel allowed the ______ plants to mature and self-pollinate.
Their offspring were called the __________ ________ ___________ (___)
Mendel's Observations:
_______of the plants were tall, _______ of the plants were short
Mendel's Conclusion:
Offspring inherit two __________ for each characteristic (e.g. height), one from each
parent,
the F1 did ________________ contrasting factors but only the dominant factor is
expressed
The Principle of Segregation:
•Hereditary characteristics are determined by distinct factors (genes) that occur
________________.
•These paired factors segregate from one another and are distributed into different
_____________.
•Each sex cell has an ________________ probability of possessing either of the pair.
Genes
Units of information about ____________ ______________
________________ from parents to offspring
Each has a specific ________________ (locus) on a chromosome
Alleles
Different molecular forms of a _________________
Arise by _______________
Dominant allele _________________ a recessive allele that is paired with it
Allele Combinations
Homozygous: having two ________________ alleles at a locus, AA or aa
Heterozygous: having two ________________ alleles at a locus, Aa
Genotype & Phenotype
Genotype refers to particular ____________ an individual carries
Phenotype refers to an individual’s ________________ __________
Cannot always determine ____________ by observing __________
Tracking Generations
Parental generation
mates to produce
First-generation offspring
mate to produce
Second-generation offspring
_____
_____
_____
Impact of Mendel’s Work
Mendel presented his results in 1865 to a __________ _______________ audience
Paper received ____________ notice and was _________ understood
Mendel discontinued his experiments in ______________
Paper rediscovered in _____________ and finally appreciated
Earlobe Variation
Whether a person is born with __________ or _________ earlobes depends on a single
gene
Gene has two molecular forms (_____________)
Earlobe Variation
You inherited one _____________ for this gene from each parent
________________ allele specifies detached earlobes
________________ allele specifies attached lobes
Dominant & Recessive Alleles
If you have attached earlobes, you inherited two copies of the recessive allele (_____)
If you have detached earlobes, you may have either one or two copies
of the dominant allele (______ or ______)
Human Variation
Some human traits occur as a few discrete types
Earlobe attachment
Many genetic ____________________
Other traits show continuous variation
_______________, ______________________, ______________________
The Monohybrid Cross
…
Mendel’s Work, applied
 These problems will focus on
(like plant height for example)
 We will use
to determine what happens to this trait over the
course of a few generations
 This method can be used on almost all genetics problems
An Example…
 We will replicate one of Mendel’s examples.
 Cross a pure bred tall plant with a purebred dwarf plant. Use Punnett’s squares to show the
F1 and F2 generations
P1
X
Phenotype
X
Genotype
X
Possible Gametes
X
P2
Each parent in this case, each parent can only give
____ ____________ __________
Now to make the square…
The number of possible gametes per parent decides the ____________ of the square. Our example
will use a 1 x 1 square…
Analysis of the _____ Generation

This means that
of the offspring in the F1 generation will have the genotype
________. The Genotypic Ratio is _____

Knowing that T is the dominant allele, all of the offspring will have the phenotype ________.
The phenotypic ratio is _______

Our STATEMENT must say what we see:
All of the F1 pea plants are Tall

Next, we will cross two plants from the F1 generation. - Tt x Tt
Crossing the F1 Generation:
F1
Phenotype
Genotype
Possible Gametes
X
X
X
X
Note that in this case, each parent
can give _____________ of their ____________
F1
The Square:
Now, more analysis for the F2 generation
_____ of the 4 has the genotype ______, ______ have the genotype _______, and _____ has the
genotype ______. The ________________ ratio is ______:______:_______
______ of the 4 offspring will be Tall (either Tt or TT), and 1 will be short (tt). The
_______________ ratio is ____________:______________
The STATEMENT:
The ____ phenotypic ratio for ____ ___________
is ___:____ ________:_____________
You need the GENERATION, the SPECIES, and the RATIO.
The Guinea Pig problem…
 Suppose that hamster colour is determined by one gene. B (brown coat) is dominant to b
(grey coat)
 Show the F1 generation for a cross of B b x B b using Punnett’s squares
 Give the Genotypic and phenotypic ratios for each generation
Chart
Parents 
Phenotype
Genotype
Possible Gametes
X
X
X
X
Punnett’s Square:
The Genotypic Ratio is ______:_______
The Phenotypic Ratio is ____:_____
________:__________
Statement:
Tips for monohybrids
 Do each generation ____________ at a time
 What ____________ can each parent contribute?
 What are the ____________ of each square?
 Count how many of each type of offspring you will have in terms of __________
genotype and phenotye.
REMEMBER YOUR ________________
Test Cross
 What if you had a female brown guinea pig at home, and wanted to know her



GENOTYPE?
How would you be able to find out? We’d use a _______ ________
A Test Cross is crossing the unknown with a ____________ _________
In this case, you would need a male homozygous recessive…
he would have to be ________
Baby Guinea Pigs…
This was the cross: ____x_____
 We know the grey hamster is bb. But the Brown guinea pig could be BB or Bb.
 All Brown offspring means that our brown guinea pig was genotype ____, because
___________________ had the___________ _________.
Baby Guinea Pigs…the second result
This was the cross: ___x___
 Half brown and half grey offspring means that our brown guinea pig was genotype ___,
because Half got the ___ _________ and half got the ___ _____________
 Half express the ________________ trait, and half express the ________________trait.
Incomplete Dominance
•There are __________________ to the dominant-recessive pattern.
•
dominance occurs when two different
control a characteristic
but neither is
. Instead the different alleles of some genes can be
expressed in the heterozygous condition to produce an ______________ phenotype.
•For example: snapdragon colour
•R =
; r = _________
•P = red x white (
x
)
•F1: genotype = 100% _____
•F1: phenotype = 100 % ______
F1
r
r
R
r
R
R
•F2 = Rr x Rr
•F2: genotype =
% RR, ___% Rr, ___% rr
•F2: phenotype = ____% red, ____% pink, _____%
white
F2
R
r
•What colour flowers would result from the following crosses?
a) red flower x pink flower
b) white flower x pink flower
c) red flower x white flower
d) pink flower x pink flower
Use Punnett Squares to answer the questions above. Make your squares on a separate piece of paper.
Show all of your work.
Write percentage of each phenotype for the crosses below:
a)
b)
c)
d)
Co-dominance & Multiple Alleles
Genetics of Blood
Human Blood Type
 One gene location for blood type
 But, three different alleles (IA, IB, and i)
 IA and IB are co-dominant and i is recessive
Genotype
Phenotype
Type A
Type B
Type AB
Type O






6 possible genotypes
4 possible phenotypes
Type A – RBC have A protein on surfaces
Type B – RBC have B protein on surfaces
Type O – RBC have neither protein on surfaces
Type AB – RBC have both proteins on surfaces
Note: RBC
stands for red
blood cells
Co-dominance
 occurs when two different alleles for the same characteristic are fully expressed in the
phenotype (e.g. ________________)
 anther example of co-dominance is in horses and shorthorn cattle where two alleles are
expressed at the __________ ___________.
 If one parent is homozygous _______ and the other is homozygous _______, the
offspring will be a pinkish colour termed “________”, a blend of red and white.
However, each individual hair in the coat is either completely white or completely red.
Blood Type Practice Questions
1. Suppose a man with type AB blood and a woman with type O blood have a child. What are the
possible blood types of the child?
IA
IB
i
i
2. Two parents have type AB blood. What is the chance that they will have a child with type O
blood?
IA
IB
IA
IB
3. Suppose a man has type B blood and a woman has type A blood. Could they have a child with type
O blood?
IB
IA
i
i
Blood Type Compatibility
Type
A
B
O
AB
Can Give Blood To
Can Receive Blood From
Type O is the universal donor
Type AB is the universal recipient
4. Suppose that emergency surgery must be performed on a Type B patient during a blood shortage.
The patient’s mother is type O, but cannot reach the hospital in time. Would blood from the
patient’s father be suitable?
IA
i
i
IB
IB
i
i
i
Sex-Related Inheritance
Autosomal chromosomes
 chromosome pairs 1 to 22
 responsible for determining nonsexual characteristics (e.g. eye and hair colour)
Sex chromosomes
 the 23rd pair of chromosomes
 responsible for determining sex (male or female) and sex-related traits (e.g. facial
hair)
Female genotype = XX
Male genotype = XY
Sex-Linked Inheritance
Many nonsexual traits appear to be inherited along with sex (are more common in one sex
than in the other).
Why?
Y chromosome is small
 most gene locations determine sexual characteristics
X chromosome is larger
 Nearly 100 genes that control nonsexual characteristics
Example:
 the X chromosome carries the gene for colour-blindness
B = normal vision
b = colour-blind
XBXB = normal female
XBXb = female carrier of colour-blindness
XbXb = colour-blind female
XBY = normal male
XbY = colour-blind male
Questions:
1.
A woman who carries the gene for colour-blindness has a child with a man who has
normal vision. What are possible genotypes and phenotypes of the child?
2. A colour-blind man has children with a woman who has normal vision. What is the
possibility that their daughters will be colour-blind?
3. A man and his wife both have normal vision, but the daughter is colour-blind. The man
sues his wife for divorce on grounds of infidelity. You are his lawyer. What evidence
will you provide to the judge?
Dihybrid Crosses
A dihybrid question is one that deals with _________________ separate traits.
Each trait acts ________________________, but both are dealt with at the same time.
eg.
When a tall pea plant with white flowers was crossed to a dwarf pea plant with purple
flowers, all of the offspring were tall with purple flowers. Show the complete analysis of the
F1 and F2 generations.
P
X
P
pheno
geno
gametes
one piece of information about ___________________________
and one piece of information about ___________________________
Punnett’s square
genotypic ratio:
__________________________
phenotypic ratio:
_________________________
Statement: _________of the ____________ are ________ and _______________________
F1
pheno
geno
Gametes
X
F1
one piece of information about ___________________________
and one piece of information about ___________________________
genotypic ratio and phenotypic ratio
there are ___________ genotypes – ___________ different ones!
but there are only _________________ phenotypes
we can group because _____________ and ______________
The __________ ratios for ______________ and _______________________ in ___________
are shown above.
Practice Questions
•Two hybrid tall, white-flowered pea plants are crossed. What are the genotypes and phenotypes of
the offspring?
•A pure tall, hybrid purple-flowered pea plant is crossed with a hybrid tall, white-flowered pea plant.
What are the genotypes and phenotypes of the offspring?
Pedigrees
Chart that shows genetic ________________________ among individuals
The knowledge of Mendelian ______________ is used to suggest basis of inheritance for a trait
Uses standardized __________________ so that everyone understands what is being shown
SYMBOL
DEFINTION
SYMBOL
DEFINITION
X
By analyzing a pedigree you can determine the type of ________________ for the trait.
Traits are either ____________________ or _____________________.
Traits are either on the ____ chromosome or they are _________________.
1. Autosomal Recessive Inheritance
Features
both unaffected __________________ of
affected individual must be _______________
affected individuals may _________________
generations
males & females _____________________
affected
father to son transmission
______________________
2. Autosomal Dominant Inheritance
Features
_________________ of the children of an
affected parent are affected
trait does ___________________ generations
males & females ______________ affected
father to son transmission is ______________
3. X-linked Inheritance
Features
____________________ are affected
may __________________ generations
father to son transmission is
__________________________
only females can be ____________________
What type of inheritance?
1. Are both genders affected equally?
2. Is there any father to son transmission?
3. Does the trait skip generations?
Therefore this is __________________________________
1. Are both genders affected equally?
2. Is there any father to son transmission?
3. Does the trait skip generations?
Therefore this is
__________________________________
1. Are both genders affected equally?
2. Is there any father to son transmission?
3. Does the trait skip generations?
Therefore this is
__________________________________
Can we determine the genotypes of the individuals in the pedigree?
1. Start with determining the ____________________________ type.
2. Once we know this, we assign the genotype to the _____________________ individuals:
If autosomal dominant trait à the unaffected are ________
If X-linked recessive à the affected males are ________
and the affected females are _______
If is autosomal recessive, the affected individuals are ______
1a.
Construct a pedigree based on the following information.
A man with the genetic defect Wilson’s disease marries a woman who does not have the defect.
They have three children, two boys and one girl. The daughter and one of the son’s each have
Wilson’s disease. The normal son marries and has three children, a son who is normal and a set of
twins, one boy and one girl, who both have the disorder. The original man’s daughter also
marries and has three children, two boys and a girl, who are all normal. One of these boys
marries and has a daughter who suffers from Wilson’s disease.
b.
What type of inheritance pattern does the trait show? Explain your answer.
c.
Write the genotypes of each individual below their symbol on your pedigree.
Applications of Genetics
1. Genetic Screening
Genetic screening: any procedure used to identify individuals with an ___________________
risk
of passing on an ________________ disorder.
Allows people who would be at high risk of having children with a disorder the choice to
__________________, or ____________________ and abort children with a genetic
disorder.
example: screening for PKU
early detection with a blood sample allows __________________ intervention and
_____________________ or _______________________ symptoms
2. Genetic Counselling
pregnant women _____________________
parents who have already produced one genetically ________________________ child
couples from __________________________ groups for specific diseases
Background Information gathered:
______________ of problem in question
family __________________
results of examination of _______________ individual
look at role of ____________________ in expression of defect
results of any ____________________
Value:
allows doctors to make recommendations on ____________________ of problem births
allows family to control _________________________ factors that may worsen problem
allows family to join _______________________ to help them cope
3. Prenatal Diagnosis
The purpose of prenatal diagnosis is to test the ________________for a genetic problem
for
which the family is at risk
amniocentesis:
__________ weeks into pregnancy
a needle is pushed through the _______________________ wall
______________________fluid is withdrawn and centrifuged
_____________ cells in the fluid are isolated and a ____________________ is made
chorionic villus:
_________________ weeks into pregnancy
tube inserted ________________________
cells from ______________________ membrane are suctioned out
__________ cells are isolated and a _______________________ is made
A ________________ is a picture showing
all of the _____________________ in an
indivdual
4. Recombinant DNA
A _____________________ is a small circular piece of DNA in a bacteria.
A _______________________________ cuts DNA at a specific sequence of base pairs
.
A the bacteria is the _________________, the human _______________________ is placed into
the
bacteria and the bacteria makes the human ____________________.

The purpose is to produce missing __________________ to allow us to treat people
with _________________________ genes.
5. Gene Therapy
Inserting a ______________________ copy of a gene into the cells that lack the ability to
produce
their own ___________.
This transfer of genes may actually correct some hereditary ___________________.
Stem cells are ___________________________ cells
(i.e. cells that have not become cells with specific functions such as skin cells or muscle
cells).
Stem cells are used because _________________________ genes can be transferred into stem
cells,
and the stem cells could ______________________ and differentiate to produce more
cells with
the ___________________________.
6. The Human Genome Project [HGP]
The HGP was started in ___________ by scientists from about 40 different countries and the first
phase
was completed in ___________.
Results:
The human genome has _____________________ genes and approximately 3164.7 x 1012
base pairs.
About ___________________ of human DNA is considered to be ‘junk DNA’.
‘_______________ DNA’ is DNA on the human chromosomes that has __________ apparent
purpose.
7. Cloning
Cloning involves make ______________ copies of an original organism
The motive is to replicate an __________________ individual,
eg. a cow that produces extra volume or quality of milk
The clone will be genetically _______________________,
but not necessarily ________________________ identical to the parent.
GENOTYPING
First of all, the terms Rhesus positive and Rhesus negative are now, more frequently, being described as
Rh(D) positive and Rh(D) negative. This section should hopefully explain why the transition has become
necessary and, also, provide basic information about the Rhesus factor. Although the initial thought of
reading through this may seem daunting, you may prefer to come back to it if you encounter any
information which needs reinforcing. Alternatively, for an adequate understanding that can be applied to
the other sections, skip to the end of the detailed section and read the simplified explanation below.
Detailed Explanation:
We all inherit a set of three Rhesus (Rh) genes from each parent called a haplotype. You may have heard
of the c, d, e, C, D and E genes. The upper case letters denote Rh positive genes and the lower case,
negative and we inherit either a positive or negative of each gene from each parent (eg. CDe/cde, cdE/cDe
etc.). This means that we then possess two of each gene and can pass either to our offspring.
If a person is tested Rh positive, their blood is said to contain the Rhesus factor - if they are tested negative
it does not. A person possessing one or more positive Rh genes (C, D or E), anywhere in their inherited
haplotypes, has inherited the Rh factor (eg. cdE/De, cde/cDe etc.) and they are tested Rh positive - only a
person with a genotype of cde/cde is truly Rh negative.
In this respect, it is now common practice to refer only to the D gene when determining the Rh factor of a
person`s blood. The term now used is `Rh(D)` instead of just `Rhesus`. This ensures that we concentrate
solely on the D gene, or lack of it, as Rh(D) positive cells contain a substance (D antigen) capable of
stimulating Rh(D) negative blood into producing harmful antibodies. These antibodies destroy (hemolyze)
red cells containing the D antigen (Rh(D) positive cells). The c, e, C and E genes are of little importance
here, as cases where antibodies have been produced against them are very rare, although there have
been instances where this has occurred and treatment has become necessary. Information about them is
still found in pregnancy booklets.
This may help to explain why the harmful antibody produced by a Rh(D)negative woman`s immune system
against Rh(D) positive cells is called `anti-D` (anti-Rh(D) - also the name of the injection given to a woman
at delivery - see `The Purpose of Anti-Rh(D) Injections`). This injection is sometimes also referred to as
RhoGAM or Anti-D Immunoglobulin.
PLEASE NOTE: A Rh(D) positive woman would never produce an antibody against a Rh(D) negative child,
as positive blood does not produce `anti-d` - there is no anti-Rh(d).
A person is Rh(D) negative if they have inherited a d gene from each parent (d/d).
A person is Rh(D) positive if they have inherited either of the following:
- a D gene from each parent (D/D)
- a D from one parent and a d from the other (D/d or d/D)
Therefore, it is possible to have a Rh(D) negative child if the mother is Rh(D) negative and the father Rh(D)
positive. The father may have inherited both a D and d and it is possible that the baby could inherit the
negative d gene from him. As Rh(D) negative woman definitely possess two d genes, the baby would
inherit one of these from her - this combination would produce a negative child (d/d).
If the father possesses two D genes, the baby will definitely inherit a positive from him, together with the
Rh(D) negative gene (d) from the mother. This combination will produce a Rh(D) positive child.
PLEASE NOTE: If a Rh(D) negative woman is absolutely certain that her partner is also Rh(D) negative,
they will surely produce Rh(D) negative offspring and the baby will not be affected by Rh(D) problems,
even if the mother already carries Rh(D) antibodies from a previous pregnancy or miscarriage with another
partner or as a result of a transfusion using positive blood cells.
Even though both the d and D gene are referred to here, the term Rh(D) does indicate that the d gene is
not really the issue here - the test performed is to determine the presence or lack of the D gene:
If a blood test shows that you do not possess the D gene, you are described as Rh(D) negative.
If this gene is found to be present, you will be described as Rh(D) positive.
So, for example:
If your blood type is B Rhesus positive (B+), the more accurate way of describing this is B Rh(D) positive
(D gene is present).
If your blood type is A Rhesus negative (A-), it would be described as A Rh(D) negative (D gene is not
present).
So, we can now see that if you possess the D gene and are, therefore, Rh(D) positive, your blood will
contain the D antigen which stimulates Rh(D) negative blood into producing antibodies (anti-Rh(D)) against
it.
At the risk of complicating this subject even more - a man who has inherited both positive factors (D/D)
would be described as being Homozygous - meaning that every one of his sperms must contain the D
gene. If a he has both (D/d or d/D) he would be described as being Heterozygous - meaning that 50% of
his sperms contain the D gene and 50% contain d.
Simple Explanation:
Whatever our blood type (ie. A, B AB, O), we all have two Rhesus genes, called D or d, depending on
whether we are Rhesus positive or negative and babies inherit one of these from each parent.
A person is Rh(D) negative if they have inherited a d gene from each parent (d/d)
A person is Rh(D) positive if they have inherited either of the following:
- a D gene from each parent (D/D)
- a D from one parent and a d from the other (D/d or d/D)
This is why it is possible to have a Rh(D) negative child if the mother is Rh(D) negative and the father
Rh(D) positive. If the father has both a negative and a positive gene, the baby may inherit this negative
gene and, as all Rh(D) negative women have two negative genes, the baby will definitely inherit a negative
from her.
PLEASE NOTE: If a negative woman is absolutely sure that her partner is Rh(D) negative, they will surely
produce Rh(D) negative offspring and no harm can come to the baby from any Rhesus antibody the
mother`s blood may contain, even if she had already developed Rhesus Iso-immune disease before the
pregnancy.
Rh(D) positive blood contains the D antigen which stimulates Rh(D) negative blood into producing
antibodies against it. Anti-Rh(D) is also the name of the injection given after delivery (more commonly
known as `anti-D`).
PLEASE NOTE: A Rh(D) positive woman would never produce an antibody against a Rh(D) negative child,
as positive blood does not produce `anti-d` - there is no anti-Rh(d).
ANTIBODIES/ANTI-RH(D) AND THEIR EFFECTS
Antibodies against Rh(D) positive cells will be present in the mother`s bloodstream if she has previously
had a Rh(D) positive baby and received no anti-D - in my experience most unlikely - midwives are just
dying to stick a woman with an anti-D after delivery, appearing most disappointed when the baby is found
to be negative and the mother is not in need of it! Antibodies will also be present if the mother has
unknowingly had a placental bleed during pregnancy, causing fetal Rh(D) positive blood to mix with the
mother's. If the mother has previously had a miscarriage or received a transfusion where Rh(D) positive
blood was used, it is very likely that, if an adequate dose of anti-D was not administered at the time, her
blood will contain Rh(D) antibodies.
PLEASE NOTE: A placental bleed (feto-maternal hemorrhage (FMH)) can occur during any pregnancy but,
before we go any further, I would like to explain why it is much more unlikely for a woman to develop
Rhesus (Rh) problems during her first:
The first time the Rhesus immune system encounters Rh(D) positive blood cells, it produces antibodies
(IgM class antibodies) that are capable of destroying them. However, these antibodies are too large to
travel through the blood vessel linking mother and baby`s blood and cannot harm the unborn child. They
are only effective in removing the positive cells from the mother's own bloodstream. It is the second and
subsequent times such positive cells are encountered that the immune system will begin to produce a
different type of antibody (class IgG antibodies) and, each time this occurs these antibodies react more
`angrily` than the time before. Even though the `linking' blood vessel is only one cell wide, and not even the
fetal and maternal bloods can mix this way, these new antibodies are of a shape and size that can easily
pass through it, from the mother`s bloodstream to the baby. So, if a woman expecting her first child has a
placental bleed during the pregnancy, she will produce the larger antibodies which can only destroy the
positive cells circulating in her own blood. She would only start producing the more harmful antibodies if
she suffered a further placental bleed. However, this is possible and the same care should be taken during
a first pregnancy as with a second or subsequent pregnancy.
When Rh(D) positive cells find their way into a negative bloodstream for the first time, they remain
`unnoticed` for about three days. After this time, the D antigen contained in these cells begins to stimulate
the immune system into producing antibodies against them. When a woman`s own immune system has
been stimulated into producing these antibodies, she is described as having been sensitized, which means
that the first larger (IgM class) antibodies have been produced to destroy the positive red cells circulating in
her own bloodstream. The immune system then `lays in wait` for the next shower of such cells to be
encountered, ie. during a next pregnancy, so that the immediate production of the more harmful (IgG class)
antibodies can begin. This is when the woman becomes Rh(D) Iso-immune - immunized against Rh(D)
positive cells, even if they belong to her unborn child. Although the amount present may decrease over a
period of time, these antibodies will remain in her bloodstream throughout her life, waiting to destroy any
future invasion of Rh(D) positive red cells.
THE PURPOSE OF ANTI-RH(D) INJECTIONS
After delivery, a blood test is performed to determine whether the baby is Rh(D) positive or negative. If the
baby is tested Rh(D) positive, the mother will be given an injection of specially prepared anti-Rh(D), within
three days (72 hours), in order to help her own blood destroy all the positive blood cells released into the
bloodstream after the placenta comes away from the womb. This way, the blood cells are destroyed before
the three days are up and her own immune system is not provoked into producing its own anti-Rh(D).
Antibodies are only harmful if produced by the mother - the small amount injected after delivery is only
there to do the job of `mopping up` the positive blood cells before they get to the immune system - they
disappear from the bloodstream after a time.
100 micrograms of anti-Rh(D) will protect a woman from around 4ml of fetal blood. If the fetal-maternal
hemorrhage (FMH) is more than 4 ml, a higher dosage is calculated and administered.
PLEASE NOTE: An anti-Rh(D) injection given at delivery is not a vaccine and does not make a woman
immune to Rhesus (Rh) disease, but, provided she is found to be free of antibodies at the time it is
administered, it can ensure that the woman begins the next pregnancy clear of antibodies.
Some Rh(D) negative women receive injections of anti-Rh(D) during pregnancy - especially at around 28
and/or 34 weeks - these would help to prevent antibodies being produced if an unsuspected placental
bleed were to then occur, or had already occurred within the preceding 72 hours of the injection.
The amount injected is effective unless an unusually high amount of fetal blood enters the maternal
bloodstream, thus `using up` the injected antibodies. In this respect, blood tests are still necessary
throughout pregnancy to make sure that all is still well.
Each doctor follows guidelines set out by his/her own practice so a woman may find that she is not offered
this treatment. However, administering anti-Rh(D) during pregnancy has been proved beneficial and it
would be wise for a woman to discuss this with her doctor if she has any concerns about the welfare of her
baby.
PLEASE NOTE: It is highly recommended that an anti-D injection be given after any incident which could
result in red Rh(D) positive cells becoming present in the mother`s bloodstream, whether this be medical
intervention where Rh(D) blood has been used, a fall which may cause a placental bleed, or a miscarriage.
ALSO NOTE: If a woman already has antibodies present in her blood a further administration of anti-D
would be pointless and completely ineffective.
Although anti-Rh(D) is extremely effective, it is specially prepared using donor blood possessing high
amounts of antibodies, the widespread use of this treatment has led to a number of women becoming
immunized against red cell antigens unrelated to the Rhesus factor which, in rare circumstances, could
also cause problems during a pregnancy, as well as there being a delay in providing blood for the mother
herself in an emergency. However, the risks involved are outweighed enormously by the benefits of antiRh(D) and the injection should not be refused unless a woman is certain that her blood already contains
Rh(D) antibodies.
If a Rh(D) negative woman is thought to be carrying a Rh(D) positive baby whose blood group differs from
her own, you might ask why it is that her own in-built mechanism for destroying other blood types does not
eliminate these cells from her bloodstream (Allo-immunization) before the D antigen contained in the Rh(D)
positive cells stimulates her into producing Rh antibodies. While this would be so for some women, each
person`s blood reacts in so many different ways, that it should never be assumed that the cells have been
destroyed in time (within 72 hours). It is, therefore, standard procedure that every Rh(D) negative
woman has an anti-Rh(D) injection after delivery when the baby is found to be Rh(D) positive, whatever her
blood group.
IMPORTANCE OF BLOOD TESTS
At the beginning of a pregnancy, a woman`s blood is tested for the Rh(D) factor and, if she is found to be
Rh(D) negative, further tests will be performed throughout the pregnancy to ensure that her blood is not
producing Rh antibodies against her baby`s blood (see Antibodies and Their Effects).
If a bleed from the placenta should occur at any time during pregnancy and the fetal blood is Rh(D)
positive, this would result in antibodies being produced. This is why it is essential to keep a note of when
blood tests are due and what the results are. If results have not been received within a week after the test
is performed, they should be `chased up` - blood tests have been known to go astray. And, if a blood test
is missed, it is vital that another one be arranged as soon as possible.
These tests are set out at carefully planned intervals throughout pregnancy to ensure that, if any antibodies
are found in the bloodstream, the baby will not have been affected by them to such a degree that it would
present a life threatening situation. Rhesus (Rh) disease (also called Hemolytic disease or Erythroblastosis
Fetalis) takes weeks rather than days to affect the unborn child, so there would be ample time to check on
the baby`s welfare and act accordingly.
It is written in pregnancy booklets that a Rh(D) negative woman should not be left to continue her
pregnancy past her due date. The reason behind this is that, after the last carefully planned blood test, it is
expected that the baby will be born on or before that date and, rather than perform another blood test, the
baby will be delivered and any problems dealt with. It seems that this is not common practice.
In this respect, a woman who has not delivered by her due date should ask that a blood test be performed
to put her mind at rest. While her doctor may insist that this is not necessary, babies suffering from Rh(D)
disease have been known to die at full term and, even though this is a rare occurrence, this simple
precaution should be taken.
PLEASE NOTE: If a baby`s blood is Rh(D) negative, it will not contain the D antigen and, therefore, cannot
stimulate the mother`s immune system into producing antibodies throughout pregnancy or at labor and an
anti-D is not necessary. Also, any antibodies already present in the mother`s blood cannot harm the baby`s
negative cells. However, unless it is 100% certain that the partner is also Rh(D) negative, there will be no
way of knowing the baby`s Rh factor during pregnancy and regular blood tests are still of utmost
importance.
A recently developed test to determine the Rh factor of the baby by testing the amniotic fluid has been
proving very effective. However, this test is only performed if a woman is already Rh(D) Rhesus isoimmune and her partner is known to possess both a positive and negative gene (d/D or D/d). This
development is quite recent, but has proved very accurate and, although further blood tests will be
performed regularly, a woman who is found to be carrying a Rh(D) negative baby will most probably be
allowed to proceed with her pregnancy as normal.
TREATMENT
Rh(D) antibodies attack the baby`s positive blood cells by coating and bursting them (hemolyzing), causing
the baby to become slowly more and more anemic - a baby affected in this way would be described as
having Rhesus ( Rh) disease (also called Hemolytic Disease of the Newborn (HDN), Hyperbilirubinemia or
Erythroblastosis Fetalis). Each time a red blood cell is destroyed, a substance called bilirubin is released
into the amniotic fluid, which causes these waters to become increasingly yellowed as more positive cells
are destroyed.
The term `Rhesus disease` may lead you to believe that the condition is an illness which could affect the
mother`s health. This is not true - her Rh antibodies cannot attack her own negative blood cells and will lie
dormant in the bloodstream, and even decrease, until they encounter the next invasion of Rh(D) positive
cells which would contain the D antigen capable of stimulating her into producing more. The only
implications of the disease are those described on these pages and the only harm is to the unborn child.
If a blood test reveals that a dangerously high level of Rh(D) antibodies are present in the mother`s
bloodstream, an amniocentesis will be performed - a sample of the amniotic fluid is taken and run through
a machine which determines the level of bilirubin - the higher the degree of yellowing, the more the baby is
affected. The results are compared carefully to a special chart (Liley chart), which shows whether the
degree of yellowing proves the baby to be at risk.
These tests will be performed by a specialist, to whom the woman will have been quickly referred and who
deals with Rhesus disease on a very regular basis. He/she will decide what action to take depending on
the degree of anemia. The results may show that the baby is not so anemic, that action needs to be taken
at that time. However, the woman would be asked to return every two weeks, or at intervals specified by
the specialist, to retest the waters and keep a close check on how the anemia is progressing.
If, however, the results of the amniocentesis are plotted as high or higher than a line on the chart, called
the Liley line, this would indicate that the baby is at risk and a transfusion into the umbilical cord will be
performed under local anesthetic, whereby Rh(D) negative blood cells will be used to replace the positive
ones destroyed. The amount of blood cells needed is cleverly determined by testing a sample of blood
taken, by needle, from the cord (cordocentesis), guided using ultrasound. These results are quickly
analyzed and the transfusion is performed there and then, using the already inserted needle, to minimize
risk factors. This method is very successful and is sometimes repeated at intervals throughout the
pregnancy, depending on subsequent test results. However, there may be occasions where the specialist
is unable to insert the needle into the cord, or where the baby is in a position where the needle poses a risk
and, in these circumstances, the needle will be inserted into the baby's abdominal cavity and injected
slowly. Instead of being transfused directly into the baby's circulation, the blood will be absorbed over a
small period of time. The mother would have been asked to arrive at the hospital an hour or so earlier than
the transfusion is scheduled, in order that a sample of her blood can be taken and tested. This process is
called cross-matching and enables the hospital's Hematology Department to find the closest match of
donor Rh(D) negative blood. Not only does the donor blood have to be Rh(D) negative, it also has to be
screened for any antigens, other than those related to the Rhesus Factor, which would stimulate the
mother's immune system into destroying the newly transfused cells.
Although the mother's Rh antibodies cannot attack the transfused blood, the cells will diminish after a time
and another test will be required two weeks later, again, to determine the amount of negative cells the baby
needs to replace the positive ones destroyed. Even though the mother's antibody level is still checked at
each stage of the treatment, it will most definitely rise to an extremely high level after the first and further
transfusions.
It may be felt that it would be safer to deliver the baby and manage the baby's condition more directly,
especially if the woman is more than 32 weeks into her pregnancy and the baby is at risk of developing
severe Hemolytic Anemia. This is a very carefully made decision and one that depends on which situation
would give the baby a better chance of survival. As Pediatric medicine has progressed to a very high
standard, it is usually considered much safer to do this. However, if transfusions proceed until later in the
pregnancy, say, 35 weeks, this increases the chance of a successful delivery nearer to full term and
lessens the need for blood exchanges and other treatments.
If the baby is born early due to this condition, a transfusion is performed immediately to replace the baby`s
blood with negative blood cells which remain in the system for about 40 days. About 9g of the baby`s blood
is withdrawn and replaced at a time. Rh(D) negative cells are used to ensure that they cannot be harmed
while helping the baby`s system to perform normally, which they do quite efficiently. They give the baby
time to produce new positive cells, supplying enough blood to keep vital organs in good working order
while this takes place. These Rh(D) negative cells will not harm the baby`s own newly produced cells, as
there is no immune system to back them up. The blood used for this purpose is normally O Rh(D) negative
and is cross-matched in the same way, to ensure that the transfused cells have no antigens to which the
baby`s blood will take exception. Within as little as 72 hours the antibodies passed to the baby from the
mother will have been eliminated.
If the anemia does not progress to the level that would require transfusions into the womb and a
transfusion is not required at delivery, a special UV-ray lamp (Bililight) will be placed over the baby to
combat any jaundice present (phototherapy). Close monitoring will ensure that the baby`s condition
remains satisfactory.
PLEASE NOTE: Since the object of an anti-Rh(D) injection, is to prevent a woman from becoming
sensitized and so becoming Rh(D) Iso-immune, the procedure would never benefit a woman with this
condition. She will have plenty of anti-Rh(D) being manufactured by her own immune system and the
injected antibodies would simply join forces with those already resident.
ISO-IMMUNIZATION AND FUTURE PREGNANCY
As the Rh(D) antibody can cross the placenta from around 12 weeks, it is assumed that a baby would
begin to become affected by the antibodies already present in the mother`s bloodstream from this time
forward. For subsequent pregnancies a woman who is Rh(D) Iso-immune will have her blood tested at this
time to check the level of antibodies present in her blood. This is measured in International Units (I/U).
Obviously, it would be preferable to have no antibodies at all but, unfortunately, this would not be the case.
However, if the level is measured to be less than 5 I/U, no action will be taken and further blood tests will
be performed frequently to check this level. If the antibody level rises above 5 I/U, an amniocentesis is
performed and, since it is possible that the baby may be Rh(D) negative, extra fluid will also be taken and
tested at the same time to determine the Rh factor. This will also be the case if the mother is known to
already have a higher level of antibodies than 5 I/U. An amniocentesis will be performed, along with a test
to determine the baby's Rh factor, if necessary, along with an antibody check.
For reasons unknown, the woman`s antibody level still fluctuates slightly in response to a Rh(D) negative
baby - not to such a high degree as during a Rh(D) positive pregnancy and, of course, no harm would
come to a Rh(D) negative child.
Throughout the rest of the pregnancy, tests are done at intervals specified by the specialist taking care of
that particular case. The length of time between testing depends on the degree by which the baby is
affected, but can be as often as every two weeks. Also taken into consideration are the results of blood
tests performed on the mother to determine the level of Rh(D) antibodies in her blood, which will rise as a
Rh(D) positive pregnancy progresses and will be plotted on a Liley chart (see `Treatment`). It is usually at
around 20 weeks, or later, that any intervention in respect of a transfusion is necessary.
Regarding transfusions and delivery, the same applies as when a placental bleed occurs during pregnancy
(see `Treatment`), except that everybody is already totally aware of the situation and ready for action
straight away.
PLEASE NOTE: When a woman is found to be carrying Rh(D) antibodies, the pregnancy is never allowed
to go past full term. Once she has been diagnosed has being Rh(D) Iso-immune, and the specialists
become involved, they take NO chances and, as they deal with this condition everyday, they have become
experts in their field, with overwhelming success rates.
NEW TREATMENTS - TRIALS
A new treatment, whereby the mother is transfused with non-specific (normal) human antibodies, is
currently being used in trials.
If the mother's partner is known to be heterozygous (has both negative and positive genes), the baby's
Rhesus factor is determined by either chorionic villus sampling (CVS) at around 11-12 weeks or
amniocentesis at around 12-14 weeks. CVS is performed by taking a small sample of cells from the
placenta, outside the amniotic sac and analyzing it. This method is often used early into the pregnancy, as
an amniocentesis cannot always be performed at this time and the results of a CVS are available within a
few days - the results of an amniocentesis take a little longer. If the baby is found to be Rh(D) positive, the
mother will immediately receive a transfusion of these normal antibodies on a daily basis for one week,
after which the transfusions will be administered weekly until around 28 weeks. These transfusions take
around 2 hours and are stopped immediately if the mother develops any adverse reaction to the treatment,
such as a rash etc. So far, the only common side effect reported has been an occasional headache just
after treatment, which has not caused any further problems for the mother. The normal antibodies help to
protect the baby's red blood cells from the mother's harmful Rh(D) antibodies.
It has been considered that a safer option would be to begin treatment without CVS and perform an
amniocentesis a few weeks later, to determine the Rh factor of the baby. This would be a decision that
needs to be made between the specialist and the patient.
NOTE: If the mother's partner is known to be homozygous (having only Rh(D) positive genes), she will
automatically go ahead with the transfusions, as there will be no need for CVS.
The same routine checks are still used to monitor the baby throughout the pregnancy - ie. amniocenteses
and the mother's antibody check, as this treatment is still only being carried out in trials.
At present, this treatment is only offered to women whose condition has become so severe that their baby
could be at risk. The trials have so far been very successful, in that a transfusion into the womb becomes
necessary much later in pregnancy, if at all, giving the baby a far greater chance of survival.
Unfortunately, even though this treatment has been very successful in severe cases, it has not yet been
clinically proven as a definite advantage and is, therefore, very expensive and not widely available as a
result. Until a much larger number of women participating in these trials have delivered successfully, it will
be a long time before any significant benefits are seen.
Another recent success had been seen in China, where a blood test is performed on the mother, to
determine the baby's Rh factor. The immature genes from the baby are detected in her blood and
analyzed. This test has been unreliable in the first trimester (up to around 13 weeks) but very accurate
during the last two trimesters. The test will not be widely available for a while, but it is a real step forward.
This article has been reproduced with the kind permission of Angela Powell:
http://freespace.virgin.net/angela.powell/rhesusfactor.htm
For further information regarding the Rh Factor visit Kenneth J. Moise, Jr., M.D. page at:
http://freespace.virgin.net/angela.powell/rhmoise.htm . Dr. Moise is well recognized as an international
authority in the area of Rhesus alloimmunization having authored 32 articles in the peer-reviewed medical
literature and 9 book chapters and invited articles.